This new project is designed to identify brain specific nucleic acids that will be useful in studies of Alzheimer disease and CJD. We will select brain specific messages that derive from specific human chromosomes. In this way we will be able to identify brain transcribed sequences that are assigned to chromosomes associated with neurological syndromes. For example, our first selection will sort out cDNAs from chromosome 21 (a chromosome thought to play an important role in Alzheimer's disease), and further selection will allow us to collect a numerically small but probably important subset of cDNAs that are essentially restricted to brain transcripts. We will use these cDNAs (on material generated Projects II, III, and V) 1) to evaluate potential modulation of specific mRNAs during the course of experimental CJD and 2) to evaluate these same mRNAs in human Alzheimer brains. These latter studies are likely to define cellular pathways that are operative in all dementias including infectious dementias and those of unknown etiology. As well pathways or patterns of expression that are specific for a subset of dementias may be defined. 3) We will also use specific chromosomal cDNAs for genomic studies of Alzheimer disease and CJD material.